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on March 10, 2003

Circulation. 2003
Published online before print March 10, 2003, doi: 10.1161/01.CIR.0000057810.48709.F6
A more recent version of this article appeared on March 25, 2003
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Submitted on October 30, 2002
Revised on December 31, 2002
Accepted on January 7, 2003

Inflammatory Markers and Risk of Heart Failure in Elderly Subjects Without Prior Myocardial Infarction. The Framingham Heart Study

Ramachandran S. Vasan MD*, Lisa M. Sullivan PhD, Ronenn Roubenoff MD, MHS, Charles A. Dinarello MD, Tamara Harris MD, MS, Emelia J. Benjamin MD, ScM, Douglas B. Sawyer MD, PhD, Daniel Levy MD, Peter W.F. Wilson MD, and Ralph B. D'Agostino PhD

From the Framingham Heart Study (R.S.V., L.S., R.B.D., E.J.B., D.L., P.W.F.W.), Framingham, Mass; Cardiology Section (R.S.V., E.J.B., D.B.S.), Myocardial Biology Unit (D.B.S.), Endocrinology Section (P.W.F.W.), Preventive Medicine and Epidemiology (R.S.V., E.J.B., D.L., P.W.F.W.), Department of Medicine, Boston University School of Medicine, Boston, Mass; the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging (R.R.) at Tufts University, Boston, Mass; the Department of Medicine, University of Colorado Health Sciences Center, Denver (C.A.D.); Geriatric Epidemiology Section, Laboratory of Epidemiology, Demography, and Biometry (T.H.), National Institute on Aging, Bethesda, Md; the National Heart, Lung, and Blood Institute (D.L.), Bethesda, Md; and the Departments of Mathematics/Statistics and Biostatistics(L.S., R.B.D.), Boston University, Boston, Mass.

* To whom correspondence should be addressed. E-mail: vasan{at}fram.nhlbi.nih.gov.

Background--Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with worse functional status and adverse prognosis. It is unclear whether cytokine levels can predict the incidence of CHF in asymptomatic individuals.

Methods and Results--We investigated the relations of serum interleukin-6 (IL-6), C-reactive protein (CRP), and spontaneous production of tumor necrosis factor-{alpha} (TNF{alpha}) by peripheral blood mononuclear cell (PBMC) to CHF incidence among 732 elderly Framingham Study subjects (mean age 78 years, 67% women) free of prior myocardial infarction and CHF. On follow-up (mean 5.2 years), 56 subjects (35 women) developed CHF. After adjustment for established risk factors, including the occurrence of myocardial infarction on follow-up, there was a 60 (PBMC TNF{alpha}) to 68% (serum IL-6) increase in risk of CHF per tertile increment in cytokine concentration (P=0.04, and 0.03, respectively, for trend). A serum CRP level >=5 mg/dL was associated with a 2.8-fold increased risk of CHF (P=0.02). Subjects with elevated levels of all 3 biomarkers (serum IL-6 and PBMC TNF{alpha} >median values, CRP>=5 mg/dL) had a markedly increased risk of CHF (hazards ratio 4.07 [95% CI 1.34 to 12.37], P=0.01) compared with the other subjects.

Conclusions--In our elderly, community-based sample, a single determination of serum inflammatory markers, particularly elevated IL-6, was associated with increased risk of CHF in people without prior myocardial infarction. Additional epidemiological investigations are warranted to confirm the contribution of inflammation to the pathogenesis of CHF in the general population.


Key words: cytokines • interleukin-6 • tumor necrosis factor-{alpha} • C-reactive protein • heart failure


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Circulation 2003 107: 1460-1462. [Extract] [Full Text]



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Diabetes CareHome page
R. M.A. Henry, O. Kamp, P. J. Kostense, A. M.W. Spijkerman, J. M. Dekker, R. van Eijck, G. Nijpels, R. J. Heine, L. M. Bouter, and C. D.A. Stehouwer
Left Ventricular Mass Increases With Deteriorating Glucose Tolerance, Especially in Women: Independence of Increased Arterial Stiffness or Decreased Flow-Mediated Dilation: The Hoorn Study
Diabetes Care, February 1, 2004; 27(2): 522 - 529.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
K. Feingold, M. S. Kim, J. Shigenaga, A. Moser, and C. Grunfeld
Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response
Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E201 - E207.
[Abstract] [Full Text] [PDF]


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Diabetes CareHome page
R. Marfella, K. Esposito, M. Siniscalchi, F. Cacciapuoti, F. Giugliano, D. Labriola, M. Ciotola, C. Di Palo, L. Misso, and D. Giugliano
Effect of Weight Loss on Cardiac Synchronization and Proinflammatory Cytokines in Premenopausal Obese Women
Diabetes Care, January 1, 2004; 27(1): 47 - 52.
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CirculationHome page
M. Cesari, B. W.J.H. Penninx, A. B. Newman, S. B. Kritchevsky, B. J. Nicklas, K. Sutton-Tyrrell, S. M. Rubin, J. Ding, E. M. Simonsick, T. B. Harris, et al.
Inflammatory Markers and Onset of Cardiovascular Events: Results From the Health ABC Study
Circulation, November 11, 2003; 108(19): 2317 - 2322.
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Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
D. R. Thomas
The Relationship Between Functional Status and Inflammatory Disease in Older Adults
J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2003; 58(11): M995 - 998.
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Cardiovasc ResHome page
N. Haramaki and H. Ikeda
Statins for heart failure: a potential for new treatment
Cardiovasc Res, November 1, 2003; 60(2): 217 - 219.
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ANN INTERN MEDHome page
R. S. Vasan, L. M. Sullivan, R. B. D'Agostino, R. Roubenoff, T. Harris, D. B. Sawyer, D. Levy, and P. W.F. Wilson
Serum Insulin-like Growth Factor I and Risk for Heart Failure in Elderly Individuals without a Previous Myocardial Infarction: The Framingham Heart Study
Ann Intern Med, October 21, 2003; 139(8): 642 - 648.
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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. B. Ware, X. Fang, and M. A. Matthay
Protein C and thrombomodulin in human acute lung injury
Am J Physiol Lung Cell Mol Physiol, September 1, 2003; 285(3): L514 - L521.
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CirculationHome page
D. R. Murray and G. L. Freeman
Proinflammatory Cytokines: Predictors of a Failing Heart?
Circulation, March 25, 2003; 107(11): 1460 - 1462.
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